Myelodysplastic syndromes
Myelodysplastic syndromes are clonal stem cell disorders producing ineffective hematopoiesis: a dysplastic, usually hypercellular bone marrow with peripheral cytopenias and a variable risk of transformation to acute myeloid leukemia. Diagnosis requires bone marrow biopsy showing dysplasia after excluding reversible mimics, risk is stratified with the IPSS-R, and treatment ranges from supportive transfusions and lenalidomide in lower-risk disease to hypomethylating agents and allogeneic transplant, the only cure, in higher-risk disease.
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What this article covers
- Overview
Definition: myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders with ineffective hematopoiesis: a usually hypercellular, dysplastic bone marrow but peripheral blood…
- Epidemiology
Age distribution: predominantly a disease of older adults, with incidence rising sharply after age 60 to 70 years.
- Risk factors
Older age: the dominant risk factor for de novo MDS.
- Pathophysiology
Clonal stem cell origin: MDS arises from an acquired somatic mutation in a hematopoietic stem cell that expands clonally and out-competes normal hematopoiesis.
- Clinical features
Macrocytic anemia: the single most common cytopenia in MDS, often with fatigue, dyspnea on exertion, and pallor; a normal vitamin B12 level helps distinguish it from nutritional macrocytic anemia.
- Differential diagnosis
Acute myeloid leukemia: shares dysplastic morphology and cytopenias, but marrow or blood blasts reach 20% or more (acute myeloid leukemia).
- Diagnosis
Establish the diagnosis with bone marrow biopsy showing dysplasia in at least 10% of a lineage, in a patient with persistent, otherwise unexplained cytopenia: this WHO-based threshold, with blast…
- Management
Confirm risk category first with the IPSS-R: lower-risk disease is managed to control cytopenias; higher-risk disease is managed to delay AML transformation and extend survival.
- Complications
Transformation to acute myeloid leukemia: the most serious complication, risk rising with higher IPSS-R category, blast percentage, and adverse cytogenetics; higher-risk patients have an approximate 25% risk of conversion in the first year.
- Prognosis
Risk category from the IPSS-R is the primary determinant of survival and AML risk: patients in low-risk categories may have a median survival of almost 9 years.
- Prevention
No primary prevention exists for de novo MDS, because it arises from age-related acquired somatic mutation; there is no validated population screening test for asymptomatic adults.
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